Development and validation of an Onchocerca ochengi adult male worm gerbil model for macrofilaricidal drug screening

PLoS Negl Trop Dis. 2019 Jul 1;13(7):e0007556. doi: 10.1371/journal.pntd.0007556. eCollection 2019 Jul.

Abstract

Background: Onchocerciasis currently afflicts an estimated 15 million people and is the second leading infectious cause of blindness world-wide. The development of a macrofilaricide to cure the disease has been hindered by the lack of appropriate small laboratory animal models. This study therefore, was aimed at developing and validating the Mongolian gerbil, as an Onchocerca ochengi (the closest in phylogeny to O. volvulus) adult male worm model.

Methodology/principal findings: Mongolian gerbils (Meriones unguiculatus) were each implanted with 20 O. ochengi male worms (collected from infected cattle), in the peritoneum. Following drug or placebo treatments, the implanted worms were recovered from the animals and analyzed for burden, motility and viability. Worm recovery in control gerbils was on average 35%, with 89% of the worms being 100% motile. Treatment of the gerbils implanted with male worms with flubendazole (FBZ) resulted in a significant reduction (p = 0.0021) in worm burden (6.0% versus 27.8% in the control animals); all recovered worms from the treated group had 0% worm motility versus 91.1% motility in control animals. FBZ treatment had similar results even after four different experiments. Using this model, we tested a related drug, oxfendazole (OFZ), and found it to also significantly (p = 0.0097) affect worm motility (22.7% versus 95.0% in the control group).

Conclusions/significance: We have developed and validated a novel gerbil O. ochengi adult male worm model for testing new macrofilaricidal drugs in vivo. It was also used to determine the efficacy of oxfendazole in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Benzimidazoles / therapeutic use
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical / methods
  • Female
  • Filaricides / therapeutic use*
  • Gerbillinae / parasitology*
  • Male
  • Mebendazole / analogs & derivatives
  • Mebendazole / therapeutic use
  • Movement
  • Onchocerca / drug effects*
  • Onchocerciasis / parasitology
  • Onchocerciasis / veterinary*

Substances

  • Benzimidazoles
  • Filaricides
  • Mebendazole
  • oxfendazole
  • flubendazole

Grants and funding

This work was supported by grants from the Bill and Melinda Gates Foundation (www.gatesfoundation.org, grant numbers OPP1098475 and OPP1017584) awarded to FCN, JS, and SL. The funders had no role in the study design, data collection and analyses, decision to publish, or preparation of the manuscript.